Cytologic features of premalignant glandular lesions in the upper gastrointestinal tract

The cytologic findings in 13 endoscopic brushing specimens from biopsy-proven premalignant glandular lesions (PGLs) of the upper gastrointestinal tract were reviewed retrospectively. The specimens were from ten patients: three with dysplasia in Barrett's esophagus, four with gastric adenomas and three with duodenal adenomas. One dysplasia in Barrett's esophagus and four adenomas (two gastric and two duodenal) had coexisting adenocarcinomas. Most pure PGLs were characterized cytologically by cohesive three-dimensional clusters of cells with more-or-less uniformly enlarged nuclei and an increased nuclear/cytoplasmic ratio. Crowding and molding were present within these clusters; however, the cells were arranged in a somewhat orderly or palisading fashion, instead of entirely haphazardly. In cases of carcinoma coexisting with adenoma or dysplasia, the atypical cells tended to be more pleomorphic and dyshesive. In one specimen from an adenocarcinoma arising in an adenoma, the adenomatous and carcinomatous components could be distinguished cytologically.     

Colonization of the porcine gastrointestinal tract by lactobacilli

Eight strains of lactobacillus isolated from the porcine gastrointestinal tract were tested for their ability to adhere in vitro to cells collected from stratified squamous epithelium in the digestive tracts of newborn piglets. Piglets were inoculated with individual strains, and their digestive tracts were sampled at intervals to determine the colonizing ability of the lactobacilli. The results of the in vitro test did not predict whether a lactobacillus strain would associate with stratified squamous epithelium in the piglet digestive tract, but epithelial association in vivo appeared to be an important factor in the maintenance of lactobacillus populations in the tract. None of the lactobacillus strains used as inocula was numerically dominant in the tract 7 days after inoculation of the piglets with a single dose of the bacteria.     

New antioxidant factors secreted by the gastrointestinal tract

It is shown, that the cells of gastric and small intestinal tissues synthesize the unidentified compounds, which suppress the peroxidation of lipids in the renal, hepatic and brain tissues. The gastric factor is thermostabile, while the intestinal factor is partially thermolabile. In case of gastrointestinal pathology the activity of these factors is reduced. It is supposed that these factors protote the common antioxidant system of the organism, increase its immunoreactivity and prevent from the action of the destroying factors.     

Host‐microbe interaction in the gastrointestinal tract

The gastrointestinal tract is a highly complex organ in which multiple dynamic physiological processes are tightly coordinated while interacting with a dense and extremely diverse microbial population. From establishment in early life, through to host‐microbe symbiosis in adulthood, the gut microbiota plays a vital role in our development and health. The effect of the microbiota on gut development and physiology is highlighted by anatomical and functional changes in germ‐free mice, affecting the gut epithelium, immune system and enteric nervous system. Microbial colonisation promotes competent innate and acquired mucosal immune systems, epithelial renewal, barrier integrity, and mucosal vascularisation and innervation. Interacting or shared signalling pathways across different physiological systems of the gut could explain how all these changes are coordinated during postnatal colonisation, or after the introduction of microbiota into germ‐free models. The application of cell‐based in‐vitro experimental systems and mathematical modelling can shed light on the molecular and signalling pathways which regulate the development and maintenance of homeostasis in the gut and beyond.     

Absorption of alpha-ketoglutarate by the gastrointestinal tract of pigs

Only a small percentage of alpha-ketoglutarate (AKG) administered lumenally to pigs appears in the portal circulation. This has been attributed to mucosal metabolism, and possibly by limited absorption. Although transporters for di- and tricarboxylic acids, which includes the sodium-dependent transporter NaDC-1, have been detected in the small intestine, correlations with functional assays are lacking. Therefore, intact tissues from three regions of the small intestine, stomach, and colon of weaned pigs were used to measure rates of AKG absorption. Western analysis was used to detect NaDC-1 in the three regions of small intestine. Rates of AKG absorption were highest in the small intestine, lowest in the colon, and intermediate in the stomach. Immunoreactive NaDC-1 was detected in the small intestine and this coincided with a component of AKG absorption that was inhibited by AKG and succinate. In contrast, absorption of AKG was inhibitable by unlabeled AKG, but not succinate, in the stomach, and by neither in the colon. Feeding studies indicated that the amounts of AKG that might be included in practical diets for pigs would not (1) upregulate rates of AKG absorption or (2) exceed estimated capacities of the small intestine to absorb AKG. The present findings indicate that the efficacy of AKG as an alternative metabolic fuel for enterocytes to spare dietary amino acids is not limited by absorption.     

Colonization of the porcine gastrointestinal tract by lactobacilli.

Eight strains of lactobacillus isolated from the porcine gastrointestinal tract were tested for their ability to adhere in vitro to cells collected from stratified squamous epithelium in the digestive tracts of newborn piglets. Piglets were inoculated with individual strains, and their digestive tracts were sampled at intervals to determine the colonizing ability of the lactobacilli. The results of the in vitro test did not predict whether a lactobacillus strain would associate with stratified squamous epithelium in the piglet digestive tract, but epithelial association in vivo appeared to be an important factor in the maintenance of lactobacillus populations in the tract. None of the lactobacillus strains used as inocula was numerically dominant in the tract 7 days after inoculation of the piglets with a single dose of the bacteria.     

Performance of the immunochemical fecal occult blood test in predicting lesions in the lower gastrointestinal tract

Background:

Previous studies have suggested that the immunochemical fecal occult blood test has superior specificity for detecting bleeding in the lower gastrointestinal tract even if bleeding occurs in the upper tract. We conducted a large population-based study involving asymptomatic adults in Taiwan, a population with prevalent upper gastrointestinal lesions, to confirm this claim.

Methods:

We conducted a prospective cohort study involving asymptomatic people aged 18 years or more in Taiwan recruited to undergo an immunochemical fecal occult blood test, colonoscopy and esophagogastroduodenoscopy between August 2007 and July 2009. We compared the prevalence of lesions in the lower and upper gastrointestinal tracts between patients with positive and negative fecal test results. We also identified risk factors associated with a false-positive fecal test result.

Results:

Of the 2796 participants, 397 (14.2%) had a positive fecal test result. The sensitivity of the test for predicting lesions in the lower gastrointestinal tract was 24.3%, the specificity 89.0%, the positive predictive value 41.3%, the negative predictive value 78.7%, the positive likelihood ratio 2.22, the negative likelihood ratio 0.85 and the accuracy 73.4%. The prevalence of lesions in the lower gastrointestinal tract was higher among those with a positive fecal test result than among those with a negative result (41.3% v. 21.3%, p < 0.001). The prevalence of lesions in the upper gastrointestinal tract did not differ significantly between the two groups (20.7% v. 17.5%, p = 0.12). Almost all of the participants found to have colon cancer (27/28, 96.4%) had a positive fecal test result; in contrast, none of the three found to have esophageal or gastric cancer had a positive fecal test result (p < 0.001). Among those with a negative finding on colonoscopy, the risk factors associated with a false-positive fecal test result were use of antiplatelet drugs (adjusted odds ratio [OR] 2.46, 95% confidence interval [CI] 1.21–4.98) and a low hemoglobin concentration (adjusted OR 2.65, 95% CI 1.62–4.33).

Interpretation:

The immunochemical fecal occult blood test was specific for predicting lesions in the lower gastrointestinal tract. However, the test did not adequately predict lesions in the upper gastrointestinal tract.The fecal occult blood test is a convenient tool to screen for asymptomatic gastrointestinal bleeding.¹ When the test result is positive, colonoscopy is the strategy of choice to investigate the source of bleeding.^2,3 However, 13%–42% of patients can have a positive test result but a negative colonoscopy,⁴ and it has not yet been determined whether asymptomatic patients should then undergo evaluation of the upper gastrointestinal tract.Previous studies showed that the frequency of lesions in the upper gastrointestinal tract was comparable or even higher than that of colonic lesions^5–9 and that the use of esophagogastroduodenoscopy may change clinical management.^10,11 Some studies showed that evaluation of the upper gastrointestinal tract helped to identify important lesions in symptomatic patients and those with iron deficiency anemia;^12,13 however, others concluded that esophagogastroduodenoscopy was unjustified because important findings in the upper gastrointestinal tract were rare^14–17 and sometimes irrelevant to the results of fecal occult blood testing.^18–21 This controversy is related to the heterogeneity of study populations and to the limitations of the formerly used guaiac-based fecal occult blood test,^5–20 which was not able to distinguish bleeding in the lower gastrointestinal tract from that originating in the upper tract.The guaiac-based fecal occult blood test is increasingly being replaced by the immunochemical-based test. The latter is recommended for detecting bleeding in the lower gastrointestinal tract because it reacts with human globin, a protein that is digested by enzymes in the upper gastrointestinal tract.²² With this advantage, the occurrence of a positive fecal test result and a negative finding on colonoscopy is expected to decrease.We conducted a population-based study in Taiwan to verify the performance of the immunochemical fecal occult blood test in predicting lesions in the lower gastrointestinal tract and to confirm that results are not confounded by the presence of lesions in the upper tract. In Taiwan, the incidence of colorectal cancer is rapidly increasing, and Helicobacter pylori-related lesions in the upper gastrointestinal tract remain highly prevalent.²³ Same-day bidirectional endoscopies are therefore commonly used for cancer screening.²⁴ This screening strategy provides an opportunity to evaluate the performance of the immunochemical fecal occult blood test.     

Biotransformation of arsenobetaine by microorganisms from the human gastrointestinal tract

Abstract

The consumption of fish and shellfish is a major route of human exposure to arsenic (As), because they contain relatively large concentrations of organoarsenicals, in particular arsenobetaine (AB). AB is considered non-toxic because of its rapid excretion from the human body. However, previous studies on human metabolism and excretion of AB have used the compound in solution rather than considering the effects that occur during the digestion of food in the gastrointestinal tract. In this preliminary study, we used microcosms inoculated with human faecal matter to investigate the aerobic and anaerobic degradation of AB by microorganisms associated with the large intestine. Samples were recovered over 30 days, centrifuged, filtered and the supernatant analysed for total As content and As speciation, using ICP–MS and HPLC–ICP–MS respectively. After 7 days the total As in the supernatants from the aerobic experiment fell to a minimum of 65% of the total added, recovering to 15% less than added after 30 days. By using anion and cation exchange chromatography coupled to ICP–MS detection, arsenobetaine (AB), dimethylarsinic acid (DMA), dimethylarsinoylacetic acid (DMAA) and trimethylarsine oxide (TMAO) were identified as degradation products. Results from the aerobic system showed that after 7 days incubation the AB had been degraded to DMA, DMAA and TMAO and after 30 days the degraded AB reappeared in the samples. The results for the anaerobic system showed no degradation of AB over the 30 day course of the experiment. These findings demonstrate for the first time that biocatalytic capability for AB degradation exists within the human gastrointestinal tract.     

Sensation in the gastrointestinal tract

There are similarities between sensation in the gastrointestinal tract (GI tract) and somatic sensation. This review concentrates on parasympathetic (vagal) components of GI sensation rather than the sympathetic (splanchnic) elements. A wide range of enteroceptors have been described over the whole length of the gut which subserve several different sensory modalities. Fibres from these enteroceptors project to the medulla, primarily to the nucleus of the solitary tract. In the medulla there is considerable integration of afferent information from different parts of the GI tract. Regulatory peptides are present both in the brain and in the GI tract. It is likely that these peptides may play a role in the modulation of sensory information in the medulla. Parallels may be drawn at a receptor level between somatic sensation and sensation in the GI tract. More centrally, sensory mechanisms relating to the gut seem less highly organized than in somatic sensation. This reduced influence of the central nervous system in GI tract sensation may be explained by the presence in the gut of a highly sophisticated intrinsic nervous system, the enteric nervous system, which pre-programmes many of the functions of the GI tract.